Urinary cell cycle arrest biomarkers and chitinase 3-like protein 1 (CHI3L1) to detect acute kidney injury in the critically ill: a post hoc laboratory analysis on the FINNAKI cohort

Abstract

Background: Acute kidney injury (AKI) is a frequently occurring syndrome in critically ill patients and is associated with worse outcomes. Biomarkers allow early identification and therapy of AKI which may improve outcomes. Urine chitinase 3-like protein 1 (uCHI3L1) was recently identified as a promising urinary biomarker for AKI. In this multicenter study, we evaluated the diagnostic performance for AKI stage 2 or greater of uCHI3L1 in comparison with the urinary cell cycle arrest biomarkers urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)•insulin-like growth factor-binding protein 7 (IGFBP7) measured by NephroCheck Risk®. Methods: Post hoc laboratory study of the prospective observational FINNAKI study. Of this cohort, we included patients with stored admission urine samples and availability of serum creatinine at day 1 of admission. Patients who already had AKI stage 2 or 3 at ICU admission were excluded. AKI was defined and staged according to the KDIGO definition and staging system. The primary endpoint was AKI stage 2 or 3 at day 1. Biomarker performance was assessed by the area under the curve of the receiver operating characteristic curve (AUC). We assessed individual performance and different combinations of urine biomarkers. Results: Of 660 included patients, 49 (7.4%) had AKI stages 2-3 at day 1. All urine biomarkers were increased at admission in AKI patients. All biomarkers and most combinations had AUCs < 0.700. The combination uCHI3L1•TIMP-2 was best with a fair AUC of 0.706 (0.670, 0.718). uCHI3L1 had a positive likelihood ratio (LR) of 2.25 which was comparable to that of the NephroCheck Risk® cutoff of 2.0, while the negative LR of 0.53 was comparable to that of the NephroCheck Risk® cutoff of 0.3.

Plasma concentrations of syndecan‐1 are dependent on kidney function

“…Urine was also collected to assess the risk of acute kidney injury by Nephrocheck ® (Astute Medical, San Diego, CA), which uses the product of 2 cell‐cycle arrest biomarkers, insulin‐like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase 2 (TIMP‐2), to calculate an index called AKIRisk ™ 8,9 . Risk values > 0.3 increase and > 2.0 greatly increase the risk of developing acute kidney injury within the subsequent 24 hours.…”

Current definition of acute kidney injury actually identifies a heterogenous group of patients with elevated serum creatinine and reduced urine output

“…Dear Editor, I read with great interest in the study by Hoste and colleagues [1], which tried to identify novel biomarkers for early diagnosis of acute kidney injury (AKI). However, I must point out that seeking novel biomarkers for the early identification of AKI by comparing the diagnostic performance of these novel biomarkers (or in combination) against AKI definition based on serum creatinine and urine output is invalid.…”

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